In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2022-12-27), p. e0279640-
Abstract:
This study employed population pharmacokinetic (popPK) models to predict levonorgestrel (LNG) and ethinyl estradiol (EE) exposure after dosing with the transdermal contraceptive TWIRLA ® (LNG/EE TDS) as a 12-week extended regimen in a healthy female population. Methods PopPK models were developed using data from a previously published phase 1, open-label, randomized clinical trial, ATI-CL14 (NCT01243580), in 36 healthy individuals. Models used cycle 2 data from 18 individuals who received the LNG/EE TDS, delivering LNG 120 μg/day and EE 30 μg/day, followed by a 1-week TDS-free period. Noncompartmental PK analyses were performed on simulated concentration–time profiles of 12 consecutive weeks of LNG/EE TDS use. Results The simulated concentration–time profiles and PK parameters for the simulated extended regimen indicated that predicted LNG and EE exposures at week 12 were similar to week 3 (predicted geometric mean EE area under the concentration-time curve from time 0 to 168 h [AUC 0-168 ] on week 3 was 0.2% lower than week 12 and LNG AUC 0-168 on week 3 was 0.9% lower than week 12), suggesting both were at steady state by week 3. Therefore, no notable accumulation beyond that at week 3 is predicted for LNG and EE following a 12-week extended regimen. The results are supported by the accumulation ratios based on maximum concentration and the area under the curve being similar at weeks 3 and 12 for LNG and EE. Conclusion These results indicate that a 12-week extended LNG/EE regimen would provide similar systemic hormonal exposure as that seen by week 3 in a standard 28-day regimen, without further hormonal accumulation. The data support the safe use of a non-daily, low-dose hormonal contraceptive in an extended regimen but should be confirmed in a clinical PK study.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0279640
DOI:
10.1371/journal.pone.0279640.g001
DOI:
10.1371/journal.pone.0279640.g002
DOI:
10.1371/journal.pone.0279640.t001
DOI:
10.1371/journal.pone.0279640.t002
DOI:
10.1371/journal.pone.0279640.t003
DOI:
10.1371/journal.pone.0279640.s001
DOI:
10.1371/journal.pone.0279640.s002
DOI:
10.1371/journal.pone.0279640.s003
DOI:
10.1371/journal.pone.0279640.s004
DOI:
10.1371/journal.pone.0279640.s005
DOI:
10.1371/journal.pone.0279640.s006
DOI:
10.1371/journal.pone.0279640.s007
DOI:
10.1371/journal.pone.0279640.r001
DOI:
10.1371/journal.pone.0279640.r002
DOI:
10.1371/journal.pone.0279640.r003
DOI:
10.1371/journal.pone.0279640.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
Permalink